Heterocyclic prostaglandins. III. Synthesis of 10-oxa-11-deoxyprostaglandin E2.

The decarboxylation of various 1-substituted-3, 7-dioxabicyclo[3.3.0]octane-2, 8-diones (2b-j) was in vestigated. On treatment with potassium acetate in aqueous pyridine under reflux, all the compounds (2b-j) examined were decarboxylated in high yields to give the corresponding trans-3-hydroxymethyl-4-butanolides (3b-j). The synthesis of 10-oxa-11-deoxyprostaglandin E2 (1a) from the compounds 3i and 3j is also described. The Moffatt oxidation of 3i and the Wittig reaction of the resulting aldehyde (6a) with dimethyl 2-oxoheptylphosphonate gave an enone (7a), which was converted into 10-oxa-11-deoxyprostaglandin E2 methyl ester (8a) and the C15-epimer (9a) by NaBH4 reduction. Hydrolysis and subsequent relactonization of 8a gave 1a in 88% yield. A similar treatment of 9a gave 1b in 87% yield. Using a similar sequence of reactions, 1a and 1b were also prepared from the nitrile analog 3j via 8b and 9b.